Abstract: SA-PO0102
A Hidden Genetic Cause of Kidney Stones: SLC34A3-Related Disease Mimicking ADPKD
Session Information
- ADPKD and Cystic Kidney Disease - 3
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Cystic (Monogenic)
Authors
- Shahreki, Elham, Geisinger Health, Danville, Pennsylvania, United States
- Chang, Alexander R., Geisinger Health, Danville, Pennsylvania, United States
Introduction
Pathogenic SLC34A3 variants cause renal phosphate wasting with hypophosphatemia, elevated 1,25-dihydroxyvitamin D, and hypercalciuria, increasing the risk of nephrolithiasis and nephrocalcinosis, often without overt bone disease (1,2). Patients with biallelic variants have a high risk of renal calcifications (~46%), with increased risk even in heterozygous carriers (1,2).
Case Description
We report a man in his 20s” with autism spectrum disorder, hypertension, and no known family history of kidney disease who initially presented in his late teens with gross hematuriaa. Laboratory testing revealed preserved kidney function (creatinine 0.98 mg/dL) with marked hematuria. Imaging demonstrated bilateral renal cysts and right-sided nephrolithiasis, raising suspicion for atypical cystic kidney disease. He subsequently developed recurrent nephrolithiasis requiring endoscopic intervention, with stone composition of calcium oxalate (70%) and carbonate apatite (30%).
Metabolic evaluation demonstrated hypercalciuria, hyperoxaluria, and hyperuricosuria, alongside hypophosphatemia and elevated 1,25-dihydroxyvitamin D (peak 103 pg/mL). Although initially diagnosed with autosomal dominant polycystic kidney disease (ADPKD), the absence of family history and atypical biochemical profile prompted genetic testing. This revealed compound heterozygous SLC34A3 variants, including a likely pathogenic splice-site variant (c.302+2T>C) and a variant of uncertain significance (c.561-8G>A), likely in trans.Phosphate supplementation (1000 mg/day) corrected hypophosphatemia (2.0 → 3.0 mg/dL) and reduced 1,25-dihydroxyvitamin D levels (103 → 66 pg/mL), no further episodes of recurrent nephrolithiasis. Hypercalciuria improved after initiation of phosphate supplementation, with urinary calcium decreasing from 302 mg to 163 mg per day.
Prior studies show partial improvement in hypercalciuria and biochemical abnormalities with phosphate supplementation
therapy (1).
Discussion
This case highlights SLC34A3-related disease as an underrecognized cause of early-onset nephrolithiasis that can mimic or coexist with cystic kidney disease. Recognition of its characteristic biochemical signature—hypophosphatemia, elevated 1,25-dihydroxyvitamin D, and hypercalciuria—is essential to prompt appropriate genetic testing. Early identification enables targeted therapy that may prevent recurrent stone formation and improve long-term renal outcomes.
Acknowledgment
References:
1. Dasgupta D et al. Mutations in SLC34A3/NPT2c Are Associated with Kidney Stones and Nephrocalcinosis. J Am Soc Nephrol. 2014;25:2366–2375.
2. Brunkhorst M et al. Presentation and Outcome in Carriers of Pathogenic Variants in SLC34A1 and SLC34A3. Kidney Int. 2025;107:116–129.